Disease relevance of P2ry1

• Immunohistochemistry showed intense staining for P2Y1, -2, and -4 in the ganglion cell layer and the outer plexiform layer [1].
• This suggests P2Y2/4 receptors simultaneously couple to pertussis toxin-sensitive and -resistant G proteins whilst P2Y1 receptors couple to only the toxin-resistant proteins [2].
• Endothelial-mediated dilations to selective P2Y1 and P2Y2 purinoceptor agonists [2-methylthioadenosine triphosphate (2MeS-ATP) and uridine 5'-triphosphate (UTP), respectively] were evaluated in middle cerebral arteries (MCAs) of rats after 2 h of ischemia followed by 24 h of reperfusion (I/R) [3].
• The role of P2Y1 purinergic receptors and cytosolic Ca2+ in hypotonically activated osmolyte efflux from a rat hepatoma cell line [4].
• Rat pheochromocytoma (PC-12) cells are known to resemble rat sensory neurons and to possess a P2y purinoceptor [5].

High impact information on P2ry1

• Radial glial calcium waves occur spontaneously and require connexin hemichannels, P2Y1 ATP receptors, and intracellular IP3-mediated calcium release [6].
• Of particular interest is the up-regulation of gamma-aminobutyric acid(A) receptor alpha5 subunit, peripheral benzodiazepine receptor, nicotinic acetylcholine receptor alpha7 subunit, P2Y1 purinoceptor, Na(+) channel beta2 subunit, and L-type Ca(2+) channel alpha2delta-1 subunit [7].
• Time- and concentration-dependent effects of ATP-mediated PGE2 secretion were noted in sinusoidal endothelial cells, whereas the profile of the relative potencies of individual nucleotides was consistent with the presence of P2y and P1 purinergic receptors [8].
• In osteoclasts purified by micromanipulation, reverse transcription-PCR revealed the presence of P2Y1, P2Y2, and P2Y6 receptor transcripts, and application of agonists for these receptors induced the transient rise of cytosolic calcium [9].
• Low levels of NF-kappaB activation were observed in untreated rabbit osteoclasts and in those exposed to 2-methylthio ADP (P2Y1 agonist) or ATP or UTP (P2Y2 agonists) [9].

Chemical compound and disease context of P2ry1

• Whole-cell patch-clamp recordings from cultured rat dorsal root ganglion neurons demonstrated that the P2Y1 receptor agonists adenosine 5'-O-2-thiodiphosphate (ADP-beta-S) and 2-methylthio adenosine 5'-diphosphate (2-MeSADP) inhibit the alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP)-induced P2X3 receptor-currents [10].
• Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase [11].
• Adenosine evoked whole-cell potassium currents and enhanced intracellular free Ca2+ concentration ([Ca2+]i) in superior colliculus neurons through a P2Y purinoceptor linked to a pertussis toxin-insensitive G-protein, possibly Gq-protein, which is involved in a protein kinase C (PKC) activation pathway [12].
• Moreover, the inhibition of adenylyl cyclase mediated by an endogenous P2Y receptor of C6 glioma cells was not enhanced by expression of the rat P2Y1 receptor [13].
• 1. Analogues of adenine nucleotides inhibited beta-adrenoceptor-stimulated cyclic AMP accumulation in C6 rat glioma cells with a pharmacological selectivity consistent with that for involvement of a P2Y-purinoceptor [14].

Biological context of P2ry1

• Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively [15].
• The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction [15].
• Taken together, ATP acts on P2Y1 receptors coupled to Gq/11, resulting in the upregulation of oxidoreductase genes, leading to the protection of astrocytes against H2O2 [16].
• Cytoprotection against oxidative stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors [16].
• The results of the present study suggest that P2Y1 receptor may play some roles in ATP-mediated signal transductions between taste bud cells and afferent taste fibers [17].

Anatomical context of P2ry1

• P2X and P2Y purinoceptor expression in pancreas from streptozotocin-diabetic rats [18].
• P2Y1 receptors were present in intra-islet capillaries, while P2Y4 receptors were found on both alpha and beta cells [18].
• P2Y1 receptor expression in ovarian smooth muscle of both blood vessels and follicular rings did not show significant changes during the oestrus cycle or pregnancy [19].
• The P2Y1 receptor was also found on glomerular mesangial cells, the brush border membrane of the proximal straight tubule and on peritubular fibroblasts [20].
• Thus, ATP, acting on P2Y1 receptors in astrocytes, showed a protective action against H2O2 [16].

Associations of P2ry1 with chemical compounds

• Protection by ATP was inhibited by P2 receptor antagonists and was mimicked by P2Y1 receptor agonists but not by adenosine [16].
• Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors [21].
• The data provide functional evidence for P2Y1 receptors in the apical membrane of the rat proximal tubule: receptor activation impairs acidification in this nephron segment [21].
• MRS-2179, a P2Y1 receptor-specific antagonist, abolished the effect of 2MeSADP, whereas theophylline, an antagonist of adenosine (P1) receptors, did not [21].
• 2-Methylthio-ATP (0.1-10 microM), an agonist that can act at P2Y1 receptors, did not contract arteries or veins, whereas UTP, an agonist at rat P2Y2/P2Y4 receptors, contracted veins (EC(50) = 15 microM) and arteries (EC(50) = 24 microM) [22].

Physical interactions of P2ry1

• In pure ductal suspensions, ATP activated a metabotropic P2Y1 purinergic receptor coupled to phospholipase C and opened a non-specific cation channel coupled to a P2X7 receptor [23].

Regulatory relationships of P2ry1

• Furthermore, we showed by double-immunolabeling methods that P2Y1-expressing cells coexpressed both IP3R3 and SNAP-25 [17].
• Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons [10].
• Purinergic P2y receptors stimulate renin secretion by rat renal cortical slices [24].

Other interactions of P2ry1

• Of the P2 receptor subtypes examined, P2X1, P2X2 and P2Y1 receptors were found in the smooth muscle layer of intrarenal vessels [20].
• In addition, staining for P2Y1, -4, and -6 mRNA was shown in the inner nuclear layer, but was absent for the P2Y2 receptor subtype [1].
• The presence of other ATP receptors such P2Y1 or P2X2/P2X3 heteropolymers in a small fraction of the cells cannot be excluded [25].
• P2X4, P2Y1 and P2Y2 receptors on rat alveolar macrophages [26].
• 5. In conclusion, the results show that ionotropic (P2X2) and metabotropic (P2Y1) ATP receptors which occur in the CNS are activated selectively by naturally-occurring adenine dinucleotides which are known to be released with nucleotides from storage vesicles [27].

Analytical, diagnostic and therapeutic context of P2ry1

• RESULTS: RT-PCR revealed the presence of P2Y1, -2, -4, and -6 mRNA in the neural retina and the retinal pigment epithelium (RPE) and choroid [1].
• P2X2 and P2Y1 immunofluorescence in rat neostriatal medium-spiny projection neurones and cholinergic interneurones is not linked to respective purinergic receptor function [28].
• P2Y1 receptor mRNA was detected in a subset of taste bud cells by in situ hybridization [17].
• In the present study, we examined the expression patterns of P2Y1 receptor subtype by using reverse transcript polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry [17].
• Northern blot analysis was used to confirm the level of expression of P2Y1 and P2Y2 [29].

References